Caliciviruses, represented by the prototype Norwalk virus, are the major cause of acute nonbacterial epidemic gastroenteritis in humans. Our continued inability to cultivate any of the etiologic human caliciviruses of human gastrointestinal disease in cell culture has been a major research obstacle. We have used a cultivatable feline calicivirus, URB, as a model for the study of calicivirus biology and replication. The sequence of the 7.7 Kb RNA genome of the URB strain was determined from cloned cDNA fragments and this information was utilized to construct a full-length cDNA copy of the genome downstream from the T7 RNA polymerase promoter. Full-length synthetic RNA transcripts prepared from this clone were infectious when transfected into feline kidney cells, thus providing us with an opportunity to gain important insights into the replication of this family of viruses and their relationship to other positive-strand RNA viruses. Experiments are in progress utilizing the infectious feline calicivirus cDNA clone (as a surrogate for Norwalk virus) to study receptor binding, infectivity of viral RNA, mapping of gene products in the viral genome, protein processing, viral pathogenesis, and the mechanisms responsible for host cell restriction in cell culture.